Cellular communication

Cell Adhesion Molecules - Cells are attached to the basal lamina and to each other by cell
Adhesion molecules: fasten cells to their neighbors, transmit signals in and out of the cell e.g.
cells that lose their contact with the extracellular matrix via integrins have a higher rate of
apoptosis than anchored cells, and interactions between integrins and the cytoskeleton are
involved in cell movement. Families:
1. Integrins – bind to various receptors
2. Adhesion molecules of the IgG
3. Cadherins – ca2+ -dependent molecules that mediate cell-to-cell adhesion
4. Selectins – lectin-like domains that bind carbohydrates

Intercellular connections
Grouped into two:
 Junctions that fasten the cells to one another and to surrounding tissues: tight junctions
(zona occludens), desmosome and zona adherens, hemidesmosome and focal adhesions
attach cells to their basal laminas
 Junctions that permit transfer of ions and other molecules from one cell to another: gap
junctions for diffusion of small molecules <1000 Da between two neighboring cells.

TIGHT JUNCTIONS
 Tight connections between cell membranes, no space between the cells, seal off body cavities
e.g. blood-brain barrier. Consists of three main families:
1. Occluding
2. Junction adhesion molecules
3. Claudins

 Epithelial cells, each zonula adherens usually a continuous structure on basal side of the
zonula occludens, and is a major site of attachment for intracellular microfilaments. It
contains cadherins.
 Desmosomes are patches characterized by apposed thickenings of the membranes of two
adjacent cells. Attached to the thickened area in each cell are intermediate filaments.
Between the two membrane thickenings the intercellular space contains filamentous material
that includes cadherins.
 Hemidesomosomes (associate with actin for cell movement) – half-desmosomes that attach
cells to the underlying basal lamina and are connected intracellular to intermediate filaments.
They contain integrins.

GAP JUNCTIONS
 Connect plasma membrane channels connecting cytoplasm of adjacent cells: permit passage
of ions, sugars, amino acids, solutes.
 Connexin form channel pass through: ions, regulatory molecules (cyclic AMP)
 Rapid chemical & electrical communication
 In body: pancreas, some nerve cells, cardiac muscle (synchronize contractions)

INTERCELLULAR COMMUNICATION

 Cells communicate with one another via chemical messengers. Chemical messengers bind to
protein receptors on surface of cell or, in cytoplasm or nucleus, triggering sequences of
intracellular changes that produce their physiologic effects.
 3 types of intercellular communication:
1. Neural communication - neurotransmitters released at synaptic junctions from nerve cells
and act across a narrow synaptic cleft on a postsynaptic cell.
2. Endocrine communication - hormones and growth factors reach cells via the circulating
blood or the lymph
3. Paracrine communication - products of cells diffuse in the ECF to affect neighboring cells
that may be some distance away. Some cells secrete chemical messengers that in some
situations bind to receptors on the same cell, that is, the cell that secreted the messenger
(autocrine communication).
 Chemical messengers: amines, amino acids, steroids, polypeptides, and in some instances,
lipids, purine nucleotides, and pyrimidine nucleotides.
 Growth factors (peptides) – stimulate cell division, histamine – dilate blood vessels,
Prostaglandin - pancreas modifies cAMP levels - regulates metabolic activities (contraction
of blood vessel smooth muscle), Nitric oxide (NO) - relaxes smooth muscle in blood vessel
walls - decreasing blood pressure.
RECEPTORS FOR CHEMICAL MESSENGERS
 Recognition of chemical messengers by cells starts with receptor recognition.
 Chemical messengers/ proteins are not static, their numbers increase and decrease in
response to various stimuli, and their properties change with changes in physiological
conditions. When a hormone or neurotransmitter is present in excess, the number of active
receptors generally decreases (down-regulation), in the presence of a deficiency of the
chemical messenger, there is an increase in the number of active receptors (up-regulation).
 Ligand – signaling molecule that binds with specific receptor (lock and key)

MECHANISMS BY WHICH CHEMICAL MESSENGERS ACT

 Receptor-ligand interaction is the first step of cell response
 This event is transduced into secondary responses: (Surface receptors)
1. Ion channel activation
2. G-protein activation
3. Activation of enzyme activity within the cell
4. Direct activation of transcription
 Ligands such as acetylcholine bind directly to ion channels in the cell membrane, changing
their conductance. Watch video.
 Many other ligands in the ECF bind to receptors on the surface of cells and trigger the release
of intracellular mediators such as cAMP that initiate changes in cell function.
 Extracellular ligands are called “first messengers” and the intracellular mediators are called
“second messengers.”

ENZYME-LINKED
 Tyrosine kinase receptors initiate phosphorylation on tyrosine residues on complementary
receptors following ligand binding and eventually to the production of transcription factors in
the nucleus that alter gene expression
 Watch video
G PROTEINS
 Common way to translate a signal to a biologic effect inside cells by nucleotide regulatory
proteins activated after binding G proteins. When an activating signal reaches a G protein,
the protein exchanges GDP for GTP. The GTP–protein complex brings about the activating
effect of the G protein. The inherent GTPase activity of the protein then converts GTP to
GDP, restoring the G protein to an inactive resting state.

 When the ligand (square) binds to the G protein-coupled receptor in the cell membrane,
GTP replaces GDP on the α subunit. GTP- α separates from the βγ subunit and GTP- α and
βγ both activate various effectors, producing physiologic effects. The intrinsic GTPase
activity of GTP- α then coverts GTP to GDP,and the α, β, and γ subunits reassociate.

CYCLIC AMP (cyclic adenosine 3’,5’-monophosphate)

 A second messenger, formed from ATP by the the enzyme adenylyl cyclase and converted to
physiologically inactive 5'AMP by the action of the enzyme phosphodiesterase.
 Cyclic AMP activates one of the cyclic nucleotide-dependent protein kinases that catalyzes
the phosphorylation of proteins, changing their conformation and altering their activity.

PRODUCTION OF cAMP BY ADENYLYL CYCLASE

 Adenylyl cyclase is a transmembrane protein, and it crosses the membrane 12 times.
 When appropriate ligand binds to a stimulatory receptor, a GS α subunit activates one of the
adenylyl cyclases.
 Two bacterial toxins have important effects on adenylyl cyclase that are mediated by G
proteins. The A subunit of cholera toxin catalyzes the transfer of ADP ribose to an arginine
residue in the middle of the α subunit of G s. This inhibits its GTPase activity, producing
prolonged stimulation of adenylyl cyclase.
 Pertussis toxin catalyzes ADP-ribosylation of a cysteine residue near the carboxyl terminal
of the α subunit of Gi. This inhibits the function of Gi
 Watch video
Reference
Barrett, K. E., and Ganong, W. F. (2012). Ganong's review of medical physiology. New York:
McGraw-Hill Medical.